Radiohalogenated nucleosides and nucleotides are currently utilized as diagnostic and therapeutic agents, cell labeling agents, radiolabeling agents for oligonucleotides, and the like. One radiohalogentated compound of particular importance is 5-radioiodo-2'-deoxyuridine (IUdR).
The synthesis and biological activity of iododeoxyuridine was first described by Prusoff in 1959 (Biochem. Biophys. Acta 33:295-296). Prusoff's synthesis is still utilized, both with and without modification, and involves the reaction of UdR with sodium radioiodide in nitric acid (J. Labelled Comp. Radiopharm. 14:83-90(1978); CancerRes. 21:345-352(1960); J. Nucl. Med. 34:1152-1162(1983); Int. J. Appl. Radiat. Isot. 36:176-181(1981)).
While the Prusoff method established the art and paved the way for improved methods of synthesis, it and other methods relying on electrophilic substitution, are complicated and lengthy procedures which produce several radiolabeled by-products, limited overall yields (.apprxeq.50%), and low specific activity (due to unidentified uv-absorbing impurities).
Another more widely utilized method of IUdR syntheses is based on a radiohalodemercuration reaction (U.S. Pat. No. 4,851,520, Appl. Radiat. Isot. 39:335-341(1988)). This method produces higher overall yields of no-carrier-added product. However, because of the nature of the precursor, the crude IUdR recovered form the reaction mixture is contaminated with trace amounts of mercury (up to 200 ppm) and requires further purification before it may be provided to humans.
The increased demand for clinically acceptable .sup.123/125 IUdR preparations has prompted those skilled in the at to investigate other methods of synthesis which might be utilized to rapidly prepare high quality, sterile, and no-carrier-added radio-IUdR. Here-to-before, these attempts have failed. Such failures are primarily due to the underlying complexity of the problem, for example, the short reaction time required for compatibility with short-lived radioisotopes (.sup.123 I) and the difficulty of purification to obtain a suitable product.